6. Project Summary/Abstract Osteoporosis is a major and growing US heath concern. The National Osteoporosis Foundation estimates that 44 million Americans have osteoporosis or low bone mass. For many of these individuals a fragility fracture will be the first indication that they have the disease. These fractures are associated with morbidity, limitations in the activities of daily living, increased mortality, particularly in the case of hip fractures, and a financial cost to society that is estimated at $19 billion per year or more than $52 million per day. Although osteoporosis is perceived by many as a disease primarily affecting post-menopausal females, it has recently been estimated that one out of eight older male veterans has osteoporosis. This translates to a prevalence of nearly 1.2 million male veterans with osteoporosis. Based on fracture statistics and veterans demographics (more than 12 male veterans for every female veteran), approximately three times as many male veterans as female veterans are expected to experience a fragility fracture. Given these facts we believe the VA has an important responsibility to be a leading stakeholder in osteoporosis research, especially given the number of male veterans likely to experience an osteoporosis-related fractures. The most common method for osteoporosis assessment uses an X-ray based technique called Dual- energy X-ray Absorptiometry, or DXA for short. The default DXA measurements were originally proposed for use in large epidemiology studies and were not intended to be used for diagnosis or treatment of individual patients. Nevertheless, these DXA measures are routinely used by primary care physicians in osteoporosis diagnosis and treatment even though these DXA measures are not accurate predictors of bone strength or fracture risk in an individual patient. The goal of this project is to develop more accurate approaches for estimating bone strength using newly developed engineering-based techniques. The project will examine three X-ray based technologies currently used for osteoporosis assessment. For each of these technologies we will quantify the accuracy with which they can predict the experimentally measured strength of cadaver bones from 25 male and 25 female donors. For each technology we will first assess the accuracy of estimating bone strength using the default measures available for that technology. We will then used new analytical and computational tools that we have developed that we believe will result in substantial improvements in estimating bone strength and that can be used in future clinical and research studies to more accurately predict bone strength in vivo. The specific densitometry technologies to be assessed were chosen so that the results will have the broadest possible impact for clinicians, clinician scientists and researchers. The ultimate goal of this research is to provide additional and better ways to identify individuals with low bone strength who would benefit from pharmacological interventions or lifestyle changes, thereby reducing both the near-term and long-term risks and costs of osteoporosis-related fractures.